Virological rebound in human immunodeficiency virus-infected patients with or without residual viraemia: results from an extended follow-up.

Human immunodeficiency virus (HIV) -infected patients with HIV RNA loads of < 50 copies/mL were followed-up for a median (interquartile range) of 30.8 (11.7-32.9) months to study the effect of residual viraemia (RV) on virological rebound (VR). At baseline, 446 (60.3%) patients had undetectable HIV RNA (group A) and 293 (39.7%) had RV (1-49 HIV RNA copies/mL, group B) by kinetic PCR. VR occurred in 4 (0.9%) patients in group A and in 12 (4.1%) patients in group B (p 0.007). Time to VR was shorter among patients of group B (Log-rank test: p 0.003). However, the proportion of VR was extremely low also among patients with RV.

Soluble CD23 in cerebrospinal fluid: a marker of AIDS-related non-Hodgkin's lymphoma in the brain.

BACKGROUND: AIDS-related non-Hodgkin's lymphoma (NHL) includes systemic lymphomas, often with brain involvement, and primary central nervous system (CNS) lymphomas. OBJECTIVE: To examine if measurement of soluble CD23 (sCD23) in cerebrospinal fluid (CSF) is useful in the diagnosis and follow-up of AIDS-related NHL. METHOD: sCD23 was measured by enzyme-linked immunosorbent assay and EBV DNA by nested polymerase chain reaction for a group of 134 patients. The NHL group included 14 patients with primary HIV-1 CNS lymphoma, 12 patients with brain involvement of systemic HIV-1 NHL and 10 patients with systemic HIV-1 NHL without brain involvement. These were compared with HIV-1-infected patients with cerebral toxoplasmosis (19), progressive multifocal leukoencephalitis (PML; 8) and AIDS-related dementia (17) and with asymptomatic HIV-1 carriers (54) and uninfected individuals (50). The levels of sCD23 were compared with the presence of Epstein-Barr virus (EBV) DNA in CSF. RESULTS: Significantly higher levels of sCD23 were found in the CSF of the patients with brain lymphoma than in those with systemic NHL (P < 0.002) or with cerebral toxoplasmosis, PML and AIDS-related dementia (P < 0.0001). The sensitivity and specificity of sCD23 in CSF as a marker for detection of brain NHL were 77% and 94%, respectively. High levels of sCD23 were found in CSF from patients with brain NHL independently of the presence (18 out of 26) or absence (8 out of 26) of EBV DNA. CONCLUSIONS: The sCD23 in CSF of HIV-1-infected patients may represent an additional, non-invasive marker for diagnosis of brain involvement in AIDS-related NHL.

Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy: effects on cerebrospinal fluid markers of JC virus replication and immune response.

Cerebrospinal fluid (CSF) samples were examined from 7 patients infected with human immunodeficiency virus type 1 (HIV-1) who had progressive multifocal leukoencephalopathy (PML). Samples were obtained both before and after 35-365 days of highly active antiretroviral therapy (HAART). By polymerase chain reaction, JC virus (JCV) DNA was found in 6 of 7 patients at baseline but in only 1 patient after HAART. In contrast, in 25 historical control patients from whom sequential CSF specimens were obtained, no reversion from detectable to undetectable JCV DNA was observed. By use of enzyme-linked immunosorbent assay, intrathecal production of antibody to JCV-VP1 was shown in only 1 of 4 HAART recipients at baseline but in 5 of 5 patients after treatment. The neuroradiological picture improved or had stabilized in all patients after 12 months of HAART, and all were alive after a median of 646 days (range, 505-775 days). Prolonged survival after HAART for PML is associated with JCV clearance from CSF. JCV-specific humoral intrathecal immunity may play a role in this response.

Human herpesvirus 6 in cerebrospinal fluid of patients infected with HIV: frequency and clinical significance.

The objective was to evaluate the frequency of human herpesvirus 6 (HHV-6) DNA detection in the CSF of patients infected with HIV and its relation to brain disease and systemic HHV-6 infection. Nested polymerase chain reaction (PCR) was used to analyse CSF samples from 365 consecutive HIV infected patients with neurological symptoms. When available, plasma and brain tissues from patients whose CSF was HHV-6 positive were also studied. HHV-6 was found in the CSF of eight of the 365 patients (2.2%): two had type A and four type B; the HHV-6 variant could not be defined in the remaining two. All eight patients had neurological symptoms and signs related to concomitant opportunistic brain diseases, including cytomegalovirus (CMV) encephalitis in five patients whose CSF was also positive for CMV-DNA. Opportunistic infections but no other unexplained lesions were also found in the brain of all of the four patients who underwent neuropathological examination. Both HHV-6 and CMV were also detected in the plasma of respectively five and seven of seven patients whose CSF was HHV-6 positive. In conclusion, HHV-6 type A or B DNA was infrequently found in the CSF of HIV infected patients, in association with both CMV brain infection and systemic HHV-6 replication. However, no certain relation between HHV-6 and brain disease was found.

Cerebrospinal fluid HIV-1 RNA levels: correlation with HIV encephalitis.

OBJECTIVE: Neuropathological abnormalities induced by HIV-1 are not always predictable on the basis of the presence of HIV-related neurological symptoms. HIV-1 RNA load was measured in the cerebrospinal fluid (CSF) of HIV-infected patients to verify whether it could be a marker of HIV-induced neuropathology. DESIGN AND METHODS: Histopathological and immunohistochemical examination of the brain for HIV-1 p24 antigen was performed in 50 HIV-infected patients with neurological symptoms; patients were defined as having HIV encephalitis in the presence of HIV-related lesions or HIV-1 p24 antigen-positive cells. Quantitative polymerase chain reaction for HIV-1 RNA was retrospectively applied to CSF samples that had been drawn 1-60 days prior to death from these 50 patients; paired plasma samples of 28 patients were also analysed. RESULTS: The CSF HIV-1 RNA copy numbers were significantly higher in 22 patients with HIV encephalitis than in 28 patients without (median, 4.77 log10 versus 3.45 log10 copies/ml; P = 0.0003). No correlation was found between CSF HIV-1 RNA load and the presence of opportunistic brain pathologies at post-mortem examination or between HIV-1 RNA loads in paired CSF and plasma samples. CONCLUSIONS: High CSF HIV-1 RNA levels are associated with HIV encephalitis, regardless of the presence of opportunistic brain diseases or HIV-1 RNA levels in plasma. Quantitative CSF HIV-1 RNA may therefore be used as a specific marker of HIV-induced neuropathology.

The application of the polymerase chain reaction of cerebrospinal fluid in the clinical management of AIDS-related CNS disorders.

In AIDS patients central nervous system (CNS) illness may be caused by HIV disease itself or by opportunistic agents, resulting in serious morbidity such as behavioral and motor disturbances, meningitis or encephalitis, among other disorders. Early diagnosis can allow specific treatment (e.g., antimicrobial treatment) that may prevent, ameliorate, or slow the catastrophic sequelae of infection, as well as reduce the need for expensive diagnostic procedures. Conventional microbiology techniques have proven inadequate for the diagnosis of most AIDS-related CNS diseases. However, the development in the past decade of the application of polymerase chain reaction (PCR) to clinical specimens has facilitated the early diagnosis of a number of infectious diseases in these patients. The technique permits the amplification of target nucleic acids such that common laboratory methods may then be used for diagnosis. The application of PCR to cerebrospinal fluid for early diagnosis of AIDS-related neurologic complications has been an impressive example of the application of PCR and may form the basis of new algorithms for diagnosis and possibly the evaluation of treatment protocols.

Varicella-zoster virus (VZV) DNA in cerebrospinal fluid of patients infected with human immunodeficiency virus: VZV disease of the central nervous system or subclinical reactivation of VZV infection?

To identify varicella-zoster virus (VZV) infections of the nervous system in patients infected with human immunodeficiency virus (HIV), polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) samples from 514 consecutive HIV-infected patients with neurological disease was performed to detect VZV DNA. VZV DNA was detected in CSF of 13 (2.5%) of 514 patients. Four of 13 patients had VZV encephalitis or meningoencephalomyelitis. These four patients received intravenous acyclovir therapy; CSF became negative for VZV DNA and clinical conditions improved for two, whereas CSF remained positive for VZV DNA and clinical conditions worsened until death for two. In nine of 13 patients, the neurological symptoms were likely caused by other simultaneous HIV-related complications in the central nervous system. After intravenous therapy with high doses of acyclovir or foscarnet, VZV was cleared from CSF in eight of nine patients. VZV DNA can be detected in CSF of HIV-infected patients in association with either manifestations of neurological VZV disease or subclinical reactivation of VZV infection. Antiviral treatment may be effective in suppressing VZV replication in the nervous system.